This chapter provides a brief discussion of the molecular mechanism of action and a survey of the different implementation tools, as well as test interpretation. In addition, the clinical implications of delayed-type hypersensitivity (DTH) skin testing in disease diagnosis and screening (i.e., tuberculosis) and the monitoring of specific disease progression (i.e., human immunodeficiency virus [HIV]) will be reviewed. DTH skin testing with two antigens (yeast cell suspension and polysaccharide antigens) from the same strains of Candida can produce discordant results in up to 20% of individuals. In the assessment of the cell-mediated immunity (CMI) response to recombinant gpl60 immunization in asymptomatic HIV-infected patients, the sensitivity of DTH skin testing compared to LPA was 75%. In addition, DTH skin testing can also aid in the diagnosis of many bacterial and fungal infections such as tuberculosis, leishmaniasis, histoplasmosis, blastomycosis, and aspergillosis. DTH skin testing provides a practical tool in the assessment of CMI. It can be used to establish defects in CMI, predict progression of and monitor HIV disease, test responses to vaccines, and diagnose bacterial and fungal infections. For valid interpretation of DTH testing, the skin test placement and accuracy of the skin test reading as well as various health factors need to be taken into consideration. Lastly, DTH correlates well with the more specific in vitro lymphoproliferative assay (LPA), and it remains the recommended initial screening tool for CMI on the basis of its ease of use and inexpensiveness.

Suggested procedure for DTH skin testing by the Mantoux method. A positive reaction (*) is signaled by an induration of ≥5 mm in response to a single antigen or an induration of ≥2 mm in response to at least two antigens; a PPD-positive reaction (#) is signaled by an induration of ≥10 mm except in HIV-infected individuals and children at high risk for tuberculosis (induration, ≥5 mm). DHST, DTH skin testing; TB, tuberculosis.

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FIGURE 1

Suggested procedure for DTH skin testing by the Mantoux method. A positive reaction (*) is signaled by an induration of ≥5 mm in response to a single antigen or an induration of ≥2 mm in response to at least two antigens; a PPD-positive reaction (#) is signaled by an induration of ≥10 mm except in HIV-infected individuals and children at high risk for tuberculosis (induration, ≥5 mm). DHST, DTH skin testing; TB, tuberculosis.

Percentage of patients having a baseline DTH response (induration, >5 mm) and developing an increase in DTH response (at least a 5-mm increase from baseline) to a given antigen after 48 weeks or more of HAART. The total numbers of patients evaluated for tetanus at baseline, week 6, week 18, and any time after baseline were 31, 23, 23, and 31, respectively. Adapted from reference 48.

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FIGURE 2

Percentage of patients having a baseline DTH response (induration, >5 mm) and developing an increase in DTH response (at least a 5-mm increase from baseline) to a given antigen after 48 weeks or more of HAART. The total numbers of patients evaluated for tetanus at baseline, week 6, week 18, and any time after baseline were 31, 23, 23, and 31, respectively. Adapted from reference 48.